Project Summary/Abstract: Tissue Pathology and Cellular Analysis Core The Translational Pathology and Cellular Analysis (TPCA) Core, will play a central role in the translational research mission of this SPORE, providing essential support for all projects by providing annotated human biospecimens and research histology services. It includes with a single-cell analysis subcore under the direction of Dr. Ken Lau. This subcore will enable technologies for quantifying and analyzing protein expression at a multiplex, single-cell level, greatly augmenting the histopathology capabilities of the TPCA on both FFPE, fresh, and frozen tissue samples. While the primary mission of the TPCA is state-of-the-art immunohistochemistry, research pathology and biorepository services, the single-cell analysis subcore will offer three cutting-edge technologies: inDrop single-cell RNA-Seq, MxIF, and DISSECT-CyTOF, and their associated computational analyses. The single-cell analysis subcore will offer services, from the preparation and processing of samples, the generation and verification of epithelial-specific reagents, screening and validation of targets, and finally, computational data analysis. Single-cell data will be synthesized and presented to investigators in adaptable formats for presentation and/or downstream analysis. A specific strength of this subcore in relation to the GI SPORE is that Dr. Ken Lau's research focus is on GI disorders and his expertise will greatly synergize with the research of GI neoplasms. We can offer highly specific molecular assays that can flexibly query a wide range of biological processes including the evaluation of signaling, cell identity, function, and behavior, all within a single cell. The TPCA will partner with other established tissue collection and immunohistochemistry shared resources, such as the Vanderbilt University Medical Center Translational Pathology Shared Resource and the Digital Histology Shared Resource, to provide exceptional services to the GI SPORE in a highly cost-effective manner. Close collaboration with the Biostatistics and Bioinformatics Core will provide the TPCA and GI SPORE with robust informatics and database tools for collection, distribution, and annotation of biospecimens in the GI SPORE repository. Dr. Washington and Dr. Lau have developed synergistic working relationships with imaging services under the direction of Dr. Charles Manning and these will be maintained between the TPCA and the Mouse and Human Molecular Imaging Core.